Immunological memory provides a fundamental basis of vaccination, yet it remains unresolved how the immune system achieves this long lasting enhanced function to re-encounters of the same pathogen. At the center of immunological memory are the memory lymphocytes that are capable of mounting a rapid and robust cellular response and have the stem cell like ability of self-renewal. These functional properties of memory T cells are acquired after activation of nave cells in which transcriptional regulation of specific genes plays a central role in the process of memory cell generation and subsequent maintenance. To understand the mechanism regulating the rapid effector function of memory CD8 T cells, we examined expression and chromatin state of a key transcription factor (eomesodermin, EOMES) and two of its targets: perforin (PRF1) and granzyme B (GZMB). Accessible chromatin associated histone 3 lysine 9 acetylation (H3K9Ac) was found significantly higher at the proximal promoter and the first exon region of all three genes in memory CD8 T cells than in nave CD8 T cells. Correspondingly, EOMES and PRF1 were constitutively higher expressed in memory CD8 T cells than in nave CD8 T cells at resting and activated states. In contrast, higher expression of GZMB was induced in memory CD8 T cells than in nave CD8 T cells only after activation. Regardless of their constitutive or inducible expression, decreased H3K9Ac levels after treatment with a histone acetyltransferase inhibitor (Curcumin) led to decreased expression of all three genes in activated memory CD8 T cells. These findings suggest that H3K9Ac associated accessible chromatin state serves as a corner stone for the differentially high expression of these effector genes in memory CD8 T cells. Thus, epigenetic changes mediated via histone acetylation may provide a chromatin memory for the rapid and robust transcriptional response of memory CD8 T cells.[unreadable] Highly activated CD4 T cell effectors can become resting after antigen clearance and go on to persist as long-lived memory cells. However, it is unclear when after antigen clearance effectors return to rest and acquire important memory properties. Here, we follow well-defined cohorts of CD4 T cells through the transitions from effector to memory by analyzing phenotype, functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 days closely resemble long-lived memory cells in terms of phenotype and function. This is true for both Th1 and Th2 lineages, and occurs whether cells rest in vivo or in vitro, suggesting a largely default pathway. Finally, we find that the transition from effector to memory at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a small cohort of genes uniquely associated with long-term memory cells. Further characterization of those genes preferentially expressed by long-term memory CD4 T cells may help to explain some of their unique features.[unreadable] Krppel-like factor 4 (Klf4) is a transcription factor and functions in regulating cell differentiation, cell growth, and cell cycle. Although Klf4 is expressed in lymphocytes, its function in lymphocytes is unknown. Here we report that the levels of Klf4 expression were low in pro-B cells and continuously increased in pre-B and in mature B cells. Upon activation, Klf4 was rapidly decreased in mature B cells after 2 hr of activation. A modest decrease in numbers of pre-B cells in bone marrow and mature B cells in spleen were observed in Klf4 deficient mice. In the absence of Klf4, fewer B cells entered S phase of the cell cycle and completed cell division in response to the engagement of BCR and/or CD40 in vitro. Furthermore, the delay in entering the cell cycle is associated with decreased expression of cyclin D2 in B cells that lack Klf4 expression. We then demonstrated that Klf4 directly bound to the promoter of cyclin D2 and regulated its expression. These findings demonstrate that Klf4 regulates B cell number and activation-induced B cell proliferation through directly acting on the promoter of cyclin D2.